An indeterminate QFT-GIT result because of undetectable or extremely low IFN-γ level in the mitogen tube suggests the presence of neutralizing anti-IFN-γ Abs in a previously healthy patient with DNTM infection.

Toll-like receptor (TLR) 2-mediated innate immunity is an important defense system against Mycobacterium tuberculosis infection. Studies on TLR2 protein expression and downstream cytokines in tuberculosis patients are lacking. TLR2 expression in the peripheral blood monocytes of 87 tuberculosis patients and 94 healthy subjects was evaluated using flow cytometry. TLR2 expression and its downstream cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon-gamma, were correlated with the clinical manifestations and outcomes of tuberculosis. The TLR2 expression in peripheral blood monocytes was higher in tuberculosis patients than in healthy subjects. Among the tuberculosis patients, those aged ≥70 years with disseminated tuberculosis or aged <70 years with symptom duration ≥14 days had lower initial TLR2 expression. After two months of treatment, TLR2 expression decreased in most patients, except in those whose sputum samples remained culture-positive for M. tuberculosis. Proportional hazards regression analyses revealed that high initial TLR2 expression and IL-10 plasma level were associated with shorter survival. TLR2 may play an important role in the course of tuberculosis. Its expression on peripheral blood monocytes and the plasma level of the downstream anti-inflammatory cytokine IL-10 may be important outcome predictors and have potential use in the management of tuberculosis patients.

The clinical features and microbiological characteristics of 315 patients with definite or possible infective endocarditis (IE) from January 1995 to December 2003 were evaluated. There were 187 males and 128 females with a mean age of 51 years (range, 1 month to 92 years). Ninety-three patients (30%) had a diagnosis of valvular heart disease and 24 (8%) had received prosthetic valve replacement. Blood culture was negative in 62 patients (20%). Staphylococci (91 patients, 32%), including methicillin-susceptible Staphylococcus aureus (15%), methicillin-resistant S. aureus (11%), and coagulase-negative staphylococci (6%), were the most commonly encountered pathogens followed by viridans group streptococci (77 patients, 24%). Eight patients (25%) had various neurological, renal, embolic, and cardiac complications. Patients with neurological complications [odds ratio (OR) 8.175, P<0.001], nosocomial IE (OR 6.661, P<0.001), underlying malignancy (OR 4.993, P<0.001), elevated serum creatinine level (OR 3.132, P=0.001), or elevated WBC count (>15000/mm3) (OR 2.537, P=0.007) were at significantly increased risk of mortality. This study found mortality from IE was associated with several factors, among which neurological complications were the most hazardous. Patients with more than one risk factor had poorer prognosis. These results suggest the need for more aggressive management in patients with IE when multiple risk factors for mortality are identified.

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Background: Mycobacterium avium complex-induced lung disease (MAC-LD) has become an important clinical concern, because its incidence has increased over the last two decades. The clinical relevance of MAC in sputum is, however, only 33∼42% because it exists in the environment ubiquitously. Therefore, MAC-LD development is supposedly indicative of host vulnerability. In particular, Toll-like receptor-2 (TLR2) programs major defense while MAC enter the airway, but the role of TLR2 is still unclear.Methods: We enrolled patients with MAC-LD and the controls. Their peripheral blood monocyte and broncho-alveolar laveage (BAL) cells were collected and we examined the expression of TLR2 pathway. In addition, we performed blocking assay and genetic polymorphism for studying the role of TLR2 receptor in MAC-LD. Results: We found that the mRNA expression of TLR2 (0.8 vs 4.1 fold-change, p=0.002) and TNF-α (5.4 vs 30.4 fold-change, p=0.065) from human peripheral monocytes were lower in the MAC-LD patients than the controls after 4 hours of MAC in-vitro infection. We examined the mRNA of TLR2 and from the BAL cells without in-vitro infection and found the fold change of mRNA was lower in the patients than the controls. By using THP-1 derived macrophages infected by MAC, TLR2 expression will increased but would be blocked significantly by SP600125, which inhibited JNK pathway. We further checked the single nucleotide polymorphism (SNP) of TLR2 gene and one was significantly associated with MAC-LD in male population with crude odds ratio (OR) of 2.750 (95% CI: 1.200­-6.304, p = 0.025) and adjusted OR of 3.050 (95% CI: 1.218-7.638, p = 0.017). In blocking TLR2 receptor in MAC infected THP-1 assay, theintracellular bacilli load increased significantly. Conclusion: The macrophage function decreases in MAC-LD patients with attenuation of TLR-2 pathway. We found a SNP of TLR2 specific to male MAC-LD and the gene-protein functional association needed further investigation.